A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection

The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure. Analysis of predictive gene features reveal little overlap among models; however, in aggregate, these genes are enriched for common pathways. Heme metabolism, the most significantly enriched pathway, is associated with a higher risk of developing symptoms following viral exposure. This study demonstrates that pre-exposure molecular predictors can be identified and improves our understanding of the mechanisms of response to respiratory viruses

A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection

The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure. Analysis of predictive gene features reveal little overlap among models; however, in aggregate, these genes are enriched for common pathways. Heme metabolism, the most significantly enriched pathway, is associated with a higher risk of developing symptoms following viral exposure. This study demonstrates that pre-exposure molecular predictors can be identified and improves our understanding of the mechanisms of response to respiratory viruses

Small RNA profiling of virus-infected grapevines: evidences for virus infection-associated and variety-specific miRNAs

Grapevine is one of the economically and culturally important perennial fruit crops. More than 60 viruses infect grapevines and adversely affect their growth and development. Latent infection of most viruses in grapevines leads to chronic modulation of gene expression at transcriptional and post-transcriptional levels. Plant small RNAs (sRNAs) consist of microRNA (miRNA) and small interfering RNA (siRNA). miRNAs are expressed from the plant genome while most siRNAs are derived from double-stranded RNA molecules which are intermediates during virus replication. In a previous study, we constructed four cDNA libraries of sRNAs that were enriched from three virus-infected grapevines and one virus-free grapevine. Majority of siRNAs align most closely with the genomes of DNA viruses in the genus Badnavirus, family Caulimoviridae that led to the discovery of a new Grapevine vein clearing virus in grapevines. In this study, we conducted a comprehensive analysis of miRNAs in the four cDNA libraries and identified novel and stress-related miRNAs. The results indicated that miRNA abundance was influenced by virus infection. A total of 54 new miRNAs were identified and characterized, six of which, VITIS-MIR17, 18, 19, 20, 21, and 22, were detected only in virus-infected samples. One target of VITIS-MIR18 is the gene coding a non-apical meristem protein (GSVIVT00035370001), a transcription factor in the regulation of plant development and stress responses. Among the virus infection-induced known miRNAs, miRNA168 and miRNA3623 likely regulate grapevine\u27s defense response, miRNA319 and miRNA395 modulate the expression of genes that are involved in nutrient metabolisms while miRNA396 plays a role in the regulation of cell division and cell cycle. The abiotic stress-induced miR169 and mi398 were negatively regulated by virus infection in grapevines. In addition, variety-specific miRNAs were discovered and compiled. The newly discovered miRNAs expand the miRNA profiles in the Vitis species. The characteristics of variety-specific and virus infection-associated miRNAs help understand the biology underlying the development and defense response of grapevines

Forecasting the Adoption Pattern of RFID in Hospitals

Technology in Healthcare sector is undergoing a fast growth compared other sectors due to the opportunity for improvement. Among the few emerging technologies implemented in hospitals Radio frequency identification (RFID) is considered to be a prominent technology. Even though RFID has been applied successfully in various sectors like retail, manufacturing etc., the adoption pattern in hospitals differs because of factors like hospital application, risk, privacy & security. This paper’s objective is to determine the adoption pattern of RFID in Healthcare considering such factors. The objective has achieved by using technology forecasting methods. The first part of the paper helps understanding the application of RFID in hospitals and provides insight into technology forecasting methods. Second part of the paper explains the execution of the methods with analysis and results derived considering RFID application in hospitals. In general this paper provides an insight towards application of RFID technology in hospitals and opens up potential options which require further research to improve application of similar technologies in healthcare

Marketing Plan Samsung Galaxy Skin

This paper attempts to develop a marketing plan for the new Smartphone to be introduced into the market by Samsung in the second quarter of 2013. After capturing a large portion of the Smartphone market share and leading the market in sales with its Galaxy S-series, Samsung will be introducing a different Smartphone that will incorporate the flexible screen technology “Galaxy Skin”. This incorporation of the flexible technology will enable Smartphones to be bendable, unbreakable, more power efficient, low weight and smaller in size. The paper introduces Samsung in general and analyzes its strength and capabilities of developing such products. Afterwards, the study covers the market demographics by sizing the total market, and the segmentation of the available market. The analysts then drill down into the market needs and investigate the target customers who have pressing need for such product. Surveys and interviews were conducted to capture the customer’s voice. The findings indicate that customers ranked the battery life to be the most favored feature followed by the flexible screen. Moreover, the analysts developed a marketing plan of the Galaxy Skin—which involved value drivers, CRTA, TALC, competition analysis, 4P’s and sales forecasting for the post launch two years. Furthermore, the price of Galaxy Skin is not yet announced, but the analysts estimated the price to be $725 based on the customer and competition analysis. Due to the secrecy practices and confidentiality that Samsung is following, the researchers of this paper had to make some assumptions such as those related to budgeting. Lastly, the analysts find that Samsung is committed to sustain its leadership in the Smartphone market by becoming the dominant developer of the flexible display technology products

Germinal Center T follicular helper (GC-Tfh) cell impairment in chronic HIV infection involves c-Maf signaling

International audienceWe have recently demonstrated that the function of T follicular helper (Tfh) cells from lymph nodes (LN) of HIV-infected individuals is impaired. We found that these cells were unable to provide proper help to germinal center (GC)-B cells, as observed by altered and inefficient anti-HIV antibody response and premature death of memory B cells. The underlying molecular mechanisms of this dysfunction remain poorly defined. Herein, we have used a unique transcriptional approach to identify these molecular defects. We consequently determined the transcriptional profiles of LN GC-Tfh cells following their interactions with LN GC-B cells from HIV-infected and HIV-uninfected individuals, rather than analyzing resting ex-vivo GC-Tfh cells. We observed that proliferating GC-Tfh cells from HIV-infected subjects were transcriptionally different than their HIV-uninfected counterparts, and displayed a significant downregulation of immune- and GC-Tfh-associated pathways and genes. Our results strongly demonstrated that MAF (coding for the transcription factor c-Maf) and its upstream signaling pathway mediators ( IL6R and STAT3 ) were significantly downregulated in HIV-infected subjects, which could contribute to the impaired GC-Tfh and GC-B cell functions reported during infection. We further showed that c-Maf function was associated with the adenosine pathway and that the signaling upstream c-Maf could be partially restored by adenosine deaminase -1 (ADA-1) supplementation. Overall, we identified a novel mechanism that contributes to GC-Tfh cell impairment during HIV infection. Understanding how GC-Tfh cell function is altered in HIV is crucial and could provide critical information about the mechanisms leading to the development and maintenance of effective anti-HIV antibodies

Differentiation into an Effector Memory Phenotype Potentiates HIV-1 Latency Reversal in CD4+ T Cells.

During antiretroviral therapy (ART), human immunodeficiency virus type 1 (HIV-1) persists as a latent reservoir in CD4+ T cell subsets in central memory (TCM), transitional memory (TTM), and effector memory (TEM) CD4+ T cells. We have identified differences in mechanisms underlying latency and responses to latency-reversing agents (LRAs) in ex vivo CD4+ memory T cells from virally suppressed HIV-infected individuals and in an in vitro primary cell model of HIV-1 latency. Our ex vivo and in vitro results demonstrate the association of transcriptional pathways of T cell differentiation, acquisition of effector function, and cell cycle entry in response to LRAs. Analyses of memory cell subsets showed that effector memory pathways and cell surface markers of activation and proliferation in the TEM subset are predictive of higher frequencies of cells carrying an inducible reservoir. Transcriptional profiling also demonstrated that the epigenetic machinery (known to control latency and reactivation) in the TEM subset is associated with frequencies of cells with HIV-integrated DNA and inducible HIV multispliced RNA. TCM cells were triggered to differentiate into TEM cells when they were exposed to LRAs, and this increase of TEM subset frequencies upon LRA stimulation was positively associated with higher numbers of p24+ cells. Together, these data highlight differences in underlying biological latency control in different memory CD4+ T cell subsets which harbor latent HIV in vivo and support a role for differentiation into a TEM phenotype in facilitating latency reversal.IMPORTANCE By performing phenotypic analysis of latency reversal in CD4+ T cells from virally suppressed individuals, we identify the TEM subset as the largest contributor to the inducible HIV reservoir. Differential responses of memory CD4+ T cell subsets to latency-reversing agents (LRAs) demonstrate that HIV gene expression is associated with heightened expression of transcriptional pathways associated with differentiation, acquisition of effector function, and cell cycle entry. In vitro modeling of the latent HIV reservoir in memory CD4+ T cell subsets identify LRAs that reverse latency with ranges of efficiency and specificity. We found that therapeutic induction of latency reversal is associated with upregulation of identical sets of TEM-associated genes and cell surface markers shown to be associated with latency reversal in our ex vivo and in vitro models. Together, these data support the idea that the effector memory phenotype supports HIV latency reversal in CD4+ T cells

Selective loss of CD107a TIGIT+ memory HIV-1-specific CD8+ T cells in PLWH over a decade of ART

The co-expression of inhibitory receptors (IRs) is a hallmark of CD8+ T-cell exhaustion (Tex) in people living with HIV-1 (PLWH). Understanding alterations of IRs expression in PLWH on long-term antiretroviral treatment (ART) remains elusive but is critical to overcoming CD8+ Tex and designing novel HIV-1 cure immunotherapies. To address this, we combine high-dimensional supervised and unsupervised analysis of IRs concomitant with functional markers across the CD8+ T-cell landscape on 24 PLWH over a decade on ART. We define irreversible alterations of IRs co-expression patterns in CD8+ T cells not mitigated by ART and identify negative associations between the frequency of TIGIT+ and TIGIT+ TIM-3+ and CD4+ T-cell levels. Moreover, changes in total, SEB-activated, and HIV-1-specific CD8+ T cells delineate a complex reshaping of memory and effector-like cellular clusters on ART. Indeed, we identify a selective reduction of HIV-1 specific-CD8+ T-cell memory-like clusters sharing TIGIT expression and low CD107a that can be recovered by mAb TIGIT blockade independently of IFNγ and IL-2. Collectively, these data characterize with unprecedented detail the patterns of IRs expression and functions across the CD8+ T-cell landscape and indicate the potential of TIGIT as a target for Tex precision immunotherapies in PLWH at all ART stages

A comprehensive platform for analyzing longitudinal multi-omics data

The analysis of longitudinal bulk and single-cell multi-omics data is a highly complex task. Here, the authors introduce PALMO, a software platform with five modules to analyse longitudinal bulk and single-cell multi-omics data, which is extensively tested in external datasets that include multiple omics modalities